Extrinsic Cues Research Articles

TMET-01. LIPID METABOLIC PROGRAMS DEFINE GLIOMA STATE IDENTITY, PLASTICITY AND DEPENDENCIES

Abstract Gliomas are lethal malignancies comprised of heterogeneous and dynamic subpopulations of cell states resembling normal neurodevelopmental cell types (radial glia (RG), oligodendrocyte progenitor cell (OPC), neuron progenitor cell (NPC), neuron, etc). While both intrinsic (genetics) and extrinsic (brain environment) cues are coupled to glioma state identity, the functional programs governing glioma cell state and plasticity are unknown. Here we performed a multi-omic interrogation of a large library (n=392) of glioma patient tumors, in vivo orthotopic xenografts and in vitro gliomasphere cultures. Comparisons of matched glioma samples across environments revealed the non-native in vitro environment constrains glioma state diversity specifically enriching for stem-like glioma cell states (RG, immune, vascular). This enrichment was linked to lipid metabolic flexibility, enabling tumors enriched for stem-like states to adapt to various tumor microenvironments. By contrast, “lineage-committed” cell states (OPC, NPC, and neuron) demonstrate restricted lipid metabolism, consequently having a dependence on lipid scavenging from the brain microenvironment for survival. These results connect intra-tumoral heterogeneity and plasticity of glioma to lipid metabolism, leveraging the functional diversity of cellular states to reveal potential therapeutic opportunities.

편의점 베이커리 외재적 단서가 태도와 구매의도에 미치는 영향

Objective : The purpose of this study is to elucidate the relationship between extrinsic cues of convenience store bakeries and attitudes and purchase intentions. Method : This study conducted a survey targeting customers who have purchased bakery products from convenience stores. A total of 400 questionnaires were distributed from August 1 to August 31, 2024. 267 questionnaires were collected and 50 of them were excluded due to unusable data. As a result, 217 questionnaires were used for hypothesis testing. Then, this study conducted a statistical analysis using SPSS 18.0, and tested the hypothesis through frequency analysis, exploratory factor analysis, and regression analysis. Results : In the case of Hypothesis 1, extrinsic cues had a positive effect on attitudes. In the case of Hypothesis 2, attitudes had a positive effect on purchase intentions. In the case of Hypothesis 3, extrinsic cues had a positive effect on purchase intentions. Implications : The results of this study emphasize the importance of extrinsic cues in establishing successful marketing strategies in the convenience store bakery market, providing implications for effectively enhancing consumer attitudes and purchase intentions.

Night shift-induced circadian disruption: links to initiation of non-alcoholic fatty liver disease/non-alcoholic steatohepatitis and risk of hepatic cancer.

The circadian system plays a crucial role in regulating metabolic homeostasis at both systemic and tissue levels by synchronizing the central and peripheral clocks with exogenous time cues, known as zeitgebers (such as the light/dark cycle). Our body's behavioral rhythms, including sleep-wake cycles and feeding-fasting patterns, align with these extrinsic time cues. The body cannot effectively rest and repair itself when circadian rhythms are frequently disrupted. In many shift workers, the internal rhythms fail to fully synchronize with the end and start times of their shifts. Additionally, exposure to artificial light at night (LAN), irregular eating patterns, and sleep deprivation contribute to circadian disruption and misalignment. Shift work and jet lag disrupt the normal circadian rhythm of liver activity, resulting in a condition known as "circadian disruption". This disturbance adversely affects the metabolism and homeostasis of the liver, contributing to excessive fat accumulation and abnormal liver function. Additionally, extended working hours, such as prolonged night shifts, may worsen the progression of non-alcoholic fatty liver disease (NAFLD) toward non-alcoholic steatohepatitis (NASH) and increase disease severity. Studies have demonstrated a positive correlation between night shift work (NSW) and elevated liver enzymes, indicative of hepatic metabolic dysfunction, potentially increasing the risk of hepatocellular carcinoma (HCC) related to NAFLD. This review consolidates research findings on circadian disruption caused by NSW, late chronotype, jet lag, and social jet lag, drawing insights from studies involving both humans and animal models that investigate the effects of these factors on circadian rhythms in liver metabolism.

CXCR4 signaling determines the fate of hematopoietic multipotent progenitors by stimulating mTOR activity and mitochondrial metabolism

Both cell-intrinsic and niche-derived, cell-extrinsic cues drive the specification of hematopoietic multipotent progenitors (MPPs) in the bone marrow, which comprise multipotent MPP1 cells and lineage-restricted MPP2, MPP3, and MPP4 subsets. Patients with WHIM syndrome, a rare congenital immunodeficiency caused by mutations that prevent desensitization of the chemokine receptor CXCR4, have an excess of myeloid cells in the bone marrow. Here, we investigated the effects of increased CXCR4 signaling on the localization and fate of MPPs. Knock-in mice bearing a WHIM syndrome–associated CXCR4 mutation ( CXCR4 1013 ) phenocopied the myeloid skewing of bone marrow in patients. Whereas MPP4 cells in wild-type mice differentiated into lymphoid cells, MPP4s in CXCR4 1013 knock-in mice differentiated into myeloid cells. This myeloid rewiring of MPP4s in CXCR4 1013 knock-in mice was associated with enhanced signaling mediated by the kinase mTOR and increased oxidative phosphorylation (OXPHOS). MPP4s also localized further from arterioles in the bone marrow of knock-in mice compared with wild-type mice, suggesting that the loss of extrinsic cues from the perivascular niche may also contribute to their myeloid skewing. Chronic treatment with the CXCR4 antagonist AMD3100 or the mTOR inhibitor rapamycin restored the lymphoid potential of MPP4s in knock-in mice. Thus, CXCR4 desensitization drives the lymphoid potential of MPP4 cells by dampening the mTOR-dependent metabolic changes that promote myeloid differentiation.

The chronobiology of human heart failure: clinical implications and therapeutic opportunities.

Circadian variation in cardiovascular and metabolic dynamics arises from interactions between intrinsic rhythms and extrinsic cues. By anticipating and accommodating adaptation to awakening and activity, their synthesis maintains homeostasis and maximizes efficiency, flexibility, and resilience. The dyssynchrony of cardiovascular load and energetic capacity arising from attenuation or loss of such rhythms is strongly associated with incident heart failure (HF). Once established, molecular, neurohormonal, and metabolic rhythms are frequently misaligned with each other and with extrinsic cycles, contributing to HF progression and adverse outcomes. Realignment of biological rhythms via lifestyle interventions, chronotherapy, and time-tailored autonomic modulation represents an appealing potential strategy for improving HF-related morbidity and mortality.

Factors influencing perceptions of processed baby foods and feeding practices among Indian mothers: a qualitative investigation

ObjectiveTo explore how professionally qualified, working Indian mothers conceptualize healthy foods in general, perceive processed infant and baby foods available commercially and what feeding practices they actually follow with their children at home.DesignFive focus groups with 8–12 participants were conducted around the participants’ conceptualization of healthy food, their perceptions about commercially available processed baby and infant foods and their actual feeding practices that they routinely follow with their children. Discussion transcripts were analyzed using an inductive coding approach.SettingIndia.ParticipantsFifty-one professionally qualified, working women with at least one child under 5 years of age.ResultsParticipants agreed that fresh food is healthiest. They also had favorable opinions about processed infant and baby foods with regards to healthfulness, hygiene and safety. Healthy foods were largely conceptualized in relation to nutrient claims, ingredients and discernible health outcomes. They use cues, such as health claims, brand, price, package design and others to determine healthfulness of the product. Perception was heavily influenced by these extrinsic cues rather than by participants’ own nutrition knowledge. Despite having the knowledge, most participants admitted to using these foods on account of factors such as their own inability to lactate, social pressure, lack of time and convenience.ConclusionsMost educated and well off people continue to use these products. While they rue the lack of stringent regulatory measures in India, they feel there is an urgent need to address this huge policy gap by way of legislation and regulation.

Soil types as extrinsic cues differentially shape sensory perception of German Riesling wine

Despite the lack of consensus regarding the effects of different soils on wine flavour, the simplification of terroir to soil type has become increasingly common in wine marketing, particularly for German Riesling. To examine the effects of this strategy on sensory perception, twenty German Rieslings from four commonly marketed soil types (Buntsandstein, Löß, Muschelkalk, and Schiefer) were evaluated for aroma, taste, and mouthfeel attributes (rate-all-that-apply) by a panel of twenty wine experts, first without and then with each wine’s soil type given as an extrinsic informational cue. While ratings from the uninformed tastings suggest baseline differences among Rieslings from the various soils, the provision of soil type cues resulted in more extensive discrimination, particularly in terms of attributes related to minerality (earthy, chalky, marine, flinty, and salty). Soil type-dependent changes in ratings suggest distinct a priori conceptions for each soil shaped the panel’s expectations and differentially altered their perception, though further work is needed to determine whether nonexpert consumers would be similarly biased by these cues. For wine soil typing to be a viable marketing strategy, a well-defined “image” of each soil would need to be communicated to consumers, to ensure their expectations are set to trigger perception of the desired sensory properties.

Enhancing organic milk sales through cumulative power of product – extrinsic cues: empirical evidence from China

PurposeTo examine the impact of manufacturer reputation, retailer reputation, and product price on consumers’ perceived quality and purchasing behavior regarding organic milk.Design/methodology/approachEmploying a 2 × 2 experiment, data were collected from 1,259 consumers in 32 provinces in China.FindingsWhen a low-reputation manufacturer sells products through a high-reputation retailer, it improves consumers’ perception of quality and positively influences their purchasing behavior. Interestingly, setting higher prices for products manufactured by low-reputation companies and selling them through high-reputation retailers did not significantly enhance consumers’ perceived quality and deter their purchasing behavior.Originality/valueThe analysis expands the framework for cue diagnosis. While the existing framework primarily focuses on the influence of cue-type combinations on perceived quality, it does not integrate purchasing behavior into the conceptual framework. This limitation hinders people understanding of the theoretical mechanisms underlying the use of cues in purchasing decisions. This paper address this by gradually introducing variables, such as retailer reputation and product price, into the baseline model, thereby extending this theory. In addition, this paper advances the marketing research literature within the business-to-business-to-consumer context by examining the additive effects of manufacturer reputation, retailer reputation, and product price on consumers’ perception of quality and purchasing behavior.

“Spicy Touch”: Cross-modal associations between hand-feel touch and capsaicin-induced oral irritation

The influence of extrinsic hand-feel touch cues on consumer experiences in food and beverage consumption is well established. However, their impact on trigeminal perception, particularly the oral irritation caused by capsaicin or spicy foods, is less understood. This study aimed to determine the existence of cross-modal associations between hand-feel touch and capsaicin-induced oral irritation. This study investigated whether these potential associations were driven by the sensory contributions of the hand-feel tactile materials (measured by instrumental physical parameters) or by affective responses (evaluated through hedonic scales and the self-reported emotion questionnaire, EsSense Profile®, by consumers). In our study, 96 participants tasted a capsaicin solution while engaging with nine hand-feel tactile materials, i.e., cardboard, linen, rattan, silicone, stainless steel, sandpaper (fine), sandpaper (rough), sponge, and towel. They subsequently rated their liking and emotional responses, perceived intensity of oral irritation, and the congruency between hand-feel tactile sensation and oral irritation. Instrumental measurements characterized the surface texture of the hand-feel tactile materials, which were correlated with the collected sensory data. The results revealed that unique cross-modal associations between hand-feel touch and capsaicin-induced oral irritation. Specifically, while sandpapers demonstrated high congruence with the sensation of oral irritation, stainless steel was found to be least congruent. These associations were influenced by both the common emotional responses (“active,” “aggressive,” “daring,” “energetic,” “guilty,” and “worried”) evoked by the hand-feel tactile materials and the capsaicin, as well as by participants’ liking for the hand-feel tactile materials and the characteristics of the surface textures. This study provides empirical evidence of the cross-modality between hand-feel tactile sensations and capsaicin-induced oral irritation, opening new avenues for future research in this area.

Meat Color, Marbling, and the Evaluation of Defects in Beef and Pork at the Point of Purchase

Intentions to purchase meat and repeat purchasing patterns will depend on the consumer’s perception of intrinsic and extrinsic quality cues. In order to discover consumers’ insights into the quality of pork and beef, the main objective of this study was to investigate meat color, marbling, and types of fresh meat defects. A total of 50 samples of meat were analyzed for three quality characteristics on different levels. This study applied a statistical calculation of a loss function invented by Taguchi. The results showed the values of variations in meat color and marbling that present the limits of consumers’ tolerance. Based on the obtained results, it was determined that the tolerable level of color variations of beef is 3.61, while for pork, this limit is 2.00. The most preferred marbling percentages were 21% and 5.74% for beef and pork, respectively. On the other hand, the negative effect of defects was the strongest for “dark cutting” for beef and “blood spotting” for pork loins.

The role of the hematopoietic stem/progenitor cells-derived extracellular vesicles in hematopoiesis

Hematopoietic stem cells (HSCs) are tightly regulated by specific microenvironments called niches to produce an appropriate number of mature blood cell types. Self-renewal and differentiation are two hallmarks of hematopoietic stem and progenitor cells, and their balance is critical for proper functioning of blood and immune cells throughout life. In addition to cell-intrinsic regulation, extrinsic cues within the bone marrow niche and systemic factors also affect the fate of HSCs. Despite this, many paracrine and endocrine factors that influence the function of hematopoietic cells remain unknown. In hematological malignancies, malignant cells remodel their niche into a permissive environment to enhance the survival of leukemic cells. These events are accompanied by loss of normal hematopoiesis. It is well known that extracellular vehicles (EVs) mediate intracellular interactions under physiological and pathological conditions. In other words, EVs transfer biological information to surrounding cells and contribute not only to physiological functions but also to the pathogenesis of some diseases, such as cancers. Therefore, a better understanding of cell-to-cell interactions may lead to identification of potential therapeutic targets. Recent reports have suggested that EVs are evolutionarily conserved constitutive mediators that regulate hematopoiesis. Here, we focus on the emerging roles of EVs in normal and pathological conditions, particularly in hematological malignancies. Owing to the high abundance of EVs in biological fluids, their potential use as biomarkers and therapeutic tools is discussed.

Identifying and Understanding the Intersectional Cues That Matter for Customers in Speed Dating Events

This study has investigated intrinsic and extrinsic intersectional cues taken into consideration by consumers when evaluating a product or a service at the intersection between the hospitality industry and the dating industries. The five main contributions of this study are as follows. First, the cue theory is a valid approach to investigate industry‐specific and intersectional products and services alike. Second, understanding of customer needs in the hospitality industry is partial, as existing research is based only on industry‐specific examples. Third, speed dating events could potentially be a competitive advantage for bars and restaurants. Fourth, online reviews are not always the most suitable and reliable data, as consumers are sometimes adopting a protective self-presentation attitude, particularly when frustrated about something. Finally, events are characterized by the types of activities participants are involved in: their level of involvement, encounters, and emotions experienced.

Growth patterns of caudal fin rays are informed by both external signals from the regenerating organ and remembered identity autonomous to the local tissue

Regenerating tissues must remember or interpret their spatial position, using this information to restore original size and patterning. The external skeleton of the zebrafish caudal fin is composed of 18 rays; after any portion of the fin is amputated, position-dependent regenerative growth restores each ray to its original length. We tested for transcriptional differences during regeneration of proximal versus distal tissues and identified 489 genes that differed in proximodistal expression. Thyroid hormone directs multiple aspects of ray patterning along the proximodistal axis, and we identified 364 transcripts showing a proximodistal expression pattern that was dependent on thyroid hormone context. To test what aspects of ray positional identity are directed by extrinsic environental cues versus remembered identity autonomous to the tissue, we transplanted distal portions of rays to proximal environments and evaluated regeneration within the new location. Native regenerating proximal tissue showed robust expression of scpp7, a transcript with thyroid-regulated proximal enrichment; in contrast, regenerating rays originating from transplanted distal tissue showed reduced (distal-like) expression during outgrowth. These distal-to-proximal transplants regenerated far beyond the length of the graft itself, indicating that cues from the proximal environment promoted additional growth. Nonetheless, these transplants initiated regeneration at a much slower rate compared to controls, suggesting memory of distal identity was retained by the transplanted tissue. This early growth retardation caused rays that originated from transplants to grow noticeably shorter than neighboring native rays. While several aspects of fin ray morphology (bifurcation, segment length) were found to be determined by the environment, we found that both regeneration speed and ray length are remembered autonomously by tissues, and that persist through multiple rounds of amputation and regeneration.

Cell wall-mediated maternal control of apical-basal patterning of the kelp Undaria pinnatifida.

The role of maternal tissue in embryogenesis remains enigmatic in many complex organisms. Here, we investigate the contribution of maternal tissue to apical-basal patterning in the kelp embryo. Focussing on Undaria pinnatifida, we studied the effects of detachment from the maternal tissue using microsurgery, staining of cell wall modifications, morphometric measurements, flow cytometry, genotyping and a modified kelp fertilisation protocol synchronising kelp embryogenesis. Detached embryos are rounder and often show aberrant morphologies. When a part of the oogonial cell wall remains attached to the zygote, the apical-basal patterning is rescued. Furthermore, the absence of contact with maternal tissue increases parthenogenesis, highlighting the critical role of maternal signals in the initial stages of development. These results show a key role for the connection to the maternal oogonial cell wall in apical-basal patterning in kelps. This observation is reminiscent of another brown alga, Fucus, where the cell wall directs the cell fate. Our findings suggest a conserved mechanism across phylogenetically distant oogamous lineages, where localised secretion of sulphated F2 fucans mediates the establishment of the apical-basal polarity. In this model, the maternal oogonial cell wall mediates basal cell fate determination by providing an extrinsic patterning cue to the future kelp embryo.

(Relative) size matters: a content analysis of front-of-packaging cue proportions and hierarchies

PurposeFront-of-packaging (FOP) is a critical branding tool that uses “cues” to communicate product attributes and establish distinct brand images. This paper aims to understand how food brands utilize cues and their relative proportions to hierarchically communicate brand image and belonging to particular subcategories.Design/methodology/approachA content analysis is used for analysing 543 food FOPs sold in Australia (breakfast cereals, chips, snack bars). Samples are collected and classified into product sub-categories defined by ingredients, consumer-audience and retail placement. A novel 10 × 10 coding grid is applied to each FOP to objectively analyse cue proportion, with statistical comparison undertaken between sub-categories.FindingsResults reveal intrinsic cues are favoured over extrinsic cues, except for those in the eatertainment sub-category. Hierarchies are evidenced that treat product and branding cues as primary, with health cues secondary. Statistically significant differences in cue proportions are consistently evident across breakfast cereals, chips and snack-bar FOPs. Clear differentiation is evidenced through cue proportions on FOP for health/nutrition focused sub-categories and eatertainment foods.Originality/value“Cue utilization theory” research is extended to an evaluation of brand encoding (not consumer decoding). Design conventions reveal how cue proportions establish a dialogue of communicating brand/product image hierarchically, the trade-offs that occur, a “meso-level” to Gestalt theory, and achieving categorization through FOP cue proportions. Deeper understanding of packaging design techniques provides inter-disciplinary insights that extend consumer behaviour, retailing and design scholarship.

Prickle2 regulates apical junction remodeling and tissue fluidity during vertebrate neurulation.

The process of folding the flat neuroectoderm into an elongated neural tube depends on tissue fluidity, a property that allows epithelial deformation while preserving tissue integrity. Neural tube folding also requires the planar cell polarity (PCP) pathway. Here, we report that Prickle2 (Pk2), a core PCP component, increases tissue fluidity by promoting the remodeling of apical junctions (AJs) in Xenopus embryos. This Pk2 activity is mediated by the unique evolutionarily conserved Ser-Thr-rich region (STR) in the carboxyterminal half of the protein. Mechanistically, the effects of Pk2 require Rac1 and are accompanied by increased cadherin dynamics and destabilization of tricellular junctions, the hotspots of AJ remodeling. Notably, Pk2 depletion leads to the accumulation of mediolaterally oriented cells in the neuroectoderm, whereas the overexpression of Pk2 or Pk1 containing the Pk2-derived STR promotes cell elongation along the anteroposterior axis. We propose that Pk2-dependent regulation of tissue fluidity contributes to anteroposterior tissue elongation in response to extrinsic cues.

Axonal endoplasmic reticulum tubules control local translation via P180/RRBP1-mediated ribosome interactions

Local mRNA translation in axons is critical for the spatiotemporal regulation of the axonal proteome. A wide variety of mRNAs are localized and translated in axons; however, how protein synthesis is regulated at specific subcellular sites in axons remains unclear. Here, we establish that the axonal endoplasmic reticulum (ER) supports axonal translation in developing rat hippocampal cultured neurons. Axonal ER tubule disruption impairs local translation and ribosome distribution. Using nanoscale resolution imaging, we find that ribosomes make frequent contacts with axonal ER tubules in a translation-dependent manner and are influenced by specific extrinsic cues. We identify P180/RRBP1 as an axonally distributed ribosome receptor that regulates local translation and binds to mRNAs enriched for axonal membrane proteins. Importantly, the impairment of axonal ER-ribosome interactions causes defects in axon morphology. Our results establish a role for the axonal ER in dynamically localizing mRNA translation, which is important for proper neuron development.

Exploring the role of the service provider in sharing economy services

PurposeThis paper aims to investigate the role of the service provider in determining customer satisfaction in sharing economy services. The authors sought to examine how the intrinsic and extrinsic cues along with their interactions influence customer satisfaction.Design/methodology/approachThis research uses a mixed-methods design to test the hypotheses. Study 1 uses secondary data from Inside Airbnb. Study 2 uses a 2 × 2 × 2 between-subject experimental design.FindingsBoth studies support the confirmation bias perspective over the expectancy-confirmation perspective in explaining the interplay among different cues in determining customer satisfaction. In the context of Airbnb, in the absence of a Superhost badge, if hosts adopt a reactive communication style, physical presence has a greater impact on customer satisfaction compared to virtual presence.Originality/valueThis study extends the services marketing literature and cue utilization theory by investigating the dynamic interactions among multiple intrinsic and extrinsic service cues. It shed new light on how a combination of these cues may become additive or redundant in determining customer satisfaction. This study contributes to the services marketing literature by addressing the interactive nature of sharing economy services and the neglected role of service providers.

PU.1 and BCL11B sequentially cooperate with RUNX1 to anchor mSWI/SNF to poise the T cell effector landscape.

Adaptive immunity relies on specialized effector functions elicited by lymphocytes, yet how antigen recognition activates appropriate effector responses through nonspecific signaling intermediates is unclear. Here we examined the role of chromatin priming in specifying the functional outputs of effector T cells and found that most of the cis-regulatory landscape active in effector T cells was poised early in development before the expression of the T cell antigen receptor. We identified two principal mechanisms underpinning this poised landscape: the recruitment of the nucleosome remodeler mammalian SWItch/Sucrose Non-Fermentable (mSWI/SNF) by the transcription factors RUNX1 and PU.1 to establish chromatin accessibility at T effector loci; and a 'relay' whereby the transcription factor BCL11B succeeded PU.1 to maintain occupancy of the chromatin remodeling complex mSWI/SNF together with RUNX1, after PU.1 silencing during lineage commitment. These mechanisms define modes by which T cells acquire the potential to elicit specialized effector functions early in their ontogeny and underscore the importance of integrating extrinsic cues to the developmentally specified intrinsic program.

Developmental Genetic and Molecular Analysis of Drosophila Central Complex Lineages.

Complex behaviors are mediated by a diverse class of neurons and glia produced during development. Both neural stem cell-intrinsic and -extrinsic temporal cues regulate the appropriate number, molecular identity, and circuit assembly of neurons. The Drosophila central complex (CX) is a higher-order brain structure regulating various behaviors, including sensory-motor integration, celestial navigation, and sleep. Most neurons and glia in the adult CX are formed during larval development by 16 Type II neural stem cells (NSCs). Unlike Type I NSCs, which directly give rise to the ganglion mother cells (GMCs), Type II NSCs give rise to multiple intermediate neural progenitors (INPs), and each INP in turn generates multiple GMCs, hence fostering the generation of longer and more diverse lineages. This makes Type II NSCs a suitable model to unravel the molecular mechanisms regulating neural diversity in more complex lineages. In this review, we elaborate on the classification and identification of NSCs based on the types of division adopted and the molecular markers expressed in each type. In the end, we discuss genetic methods for lineage analysis and birthdating. We also explain the temporal expression of stem cell factors and genetic techniques to study how stem cell factors may regulate neural fate specification.